alcohol consumption and the risk of dementia

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For personal use. Only reproduce with permission from The Lancet Publishing Group. Alcohol consumption and the risk of dementia THE LANCET Neurology Vol 2 June 2003 http://neurology.thelancet.com 333 Reflection & Reaction The possibility that alcohol may protect against age-related cognitive decline and neurodegenerative disease has been debated for more than two decades. Mild to moderate alcohol consumption—defined as one to three glasses per day—is associated with lower mortality, reduced risk of coronary heart disease, and fewer white-matter lesions. 1 Because vascular disease is implicated in the cause of both vascular and Alzheimer type dementia, there has been renewed interest in the role of alcohol, even though previous studies have been inconclusive. Studies done in the 1980s were cross-sectional in design, did not include possible confounding comorbid disorders, and produced conflicting results (odds ratios ranged from 0·5 to 2·3). Meta-analyses of these case control studies found no significant association between alcohol consumption and dementia. However, the exclusion of individuals with a history of alcoholism or cardiovascular disease was an important source of bias in many of these studies. The fact that abstinence from alcohol is commonly the result of poor health is another potential source of bias. In addition, some studies did not differentiate between the type or quantity of alcohol consumed. Several large-scale population- based studies, which accounted for both confounding and interacting risk factors in a longitudinal design, have now been done. Most of these studies have found an association of alcohol consumption with a low risk of incident dementia. More recent studies have shown that risk is high both in people who abstain from drinking and in those who consume a lot of alcohol. The Rotterdam longitudinal study 2 —which used “never drinkers” rather than recent abstainers as a reference group— concluded that risk was lowest in people who consumed one to three drinks per day. Non-health related variables must also be considered. Leibovici and co-workers 3 reported a decrease risk of dementia (odds ratio=0·26) associated with alcohol consumption. However, when place of residence was included in the model used, this effect disappeared. This is because elderly people with mild cognitive impair- ment or dementia commonly live in nursing homes where alcohol is prohibited. Studies that do not take non-alcohol related risk factors into account are therefore at risk of misclassifying participants. In a recent prospective nested cohort study, Mukamal and co- workers 4 have tried to avoid the biases of previous studies. They took repeated measurements of alcohol consumption, separated former drinkers from long-term abstainers, and tried to establish drinking behaviour up to 5 years before the start of the study. Mukamal and colleagues also attempted to obtain proxy assessment of deceased or unavailable participants. The results of the study support previous findings of a small protective effect of mild to moderate alcohol consumption on the risk of dementia. However, out of 5888 participants in the initial study, 842 were not examined, 1386 did not have an MRI examination, 52 did not complete a cognitive examination, and 107 of 480 incident cases of dementia were eliminated. People with cognitive impairment and early dementia are more likely to refuse cognitive examinations, to have difficulties in travelling to examination centres, and to drop out of community studies due to change of residence. The authors noted, for example, that individuals who completed an MRI examination were significantly healthier and consumed significantly more alcohol than those who did not. Therefore, this study may still have been open to bias. The study by Mukamal and co- workers is an improvement on previous studies for two reasons: first, the retrospective assessment of cognitive function in deceased individuals by proxy questionnaire, although such a global assessment would cover all causes of terminal cognitive decline; and second, the assessment of drinking behaviour up to 5 years before the start of the study for the identification of individuals who may have recently stopped drinking due to cognitive or other health problems. But is a 5 year time period sufficient? Because dementia in later life has been associated with high blood pressure in early adulthood, 5 do younger adults who are at a high risk of developing dementia reduce their alcohol consumption at an early age because of hypertension? Although most population-based studies have found that consumption of one to three glasses of alcohol per day decreases the risk of dementia in later life, these findings should be interpreted with great caution. Population-based studies are flawed by various problems: the diagnosis of incident dementia, the reliability of self-reports of alcohol consumption, fluctuating patterns of drinking behaviour throughout life, mortality, and drop-out bias. More importantly, if alcohol is protective, at what age is it protective? Researchers have assumed that alcohol is protective immediately before the potential onset of dementia. However, considering the adverse effects of alcohol consumption—such as stroke, cortical atrophy, driving accidents, and falls— clinicians should think carefully before prescribing several glasses of alcohol per day in the absence of a clear benefit. Karen Ritchie Institut National de la Santé et de la Recherché Médicale, E0361 Epidemiology of Nervous System Pathologies, Hôpital La Colombière, Montpellier, France. Email [email protected] References 1 Scherr PA, LaCroix AZ, Wallace RB. Light to moderate alcohol consumption and mortality in the elderly. J Am Geriatr Soc 1992; 40: 651–57. 2 Ruitenberg A, van Swieten JC, Witteman JC, et al. Alcohol consumption and risk of dementia: the Rotterdam study. Lancet 2002; 359: 281–86. 3 Leibovici D, Ritchie K, Ledésert B, Touchon J. The effects of wine and tobacco consumption on cognitive performance in the elderly: a longitudinal study of relative risk. Int J Epidemiol 1999; 28: 77–81. 4 Mukamal KJ, Kuller LH, Fitzpatrick AL, Longstreth WT, Mittleman MA, Siscovick DS. Prospective study of alcohol consumption and risk of dementia in older adults. JAMA 2003; 289: 1405–13. 5 Skoog I, Lernfelt B, Landahl S, et al. 15 year longitudinal study of blood pressure and dementia. Lancet 1996; 347: 1141–45.

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Page 1: Alcohol consumption and the risk of dementia

For personal use. Only reproduce with permission from The Lancet Publishing Group.

Alcohol consumption and the risk of dementia

THE LANCET Neurology Vol 2 June 2003 http://neurology.thelancet.com 333

Reflection & Reaction

The possibility that alcohol mayprotect against age-related cognitivedecline and neurodegenerative diseasehas been debated for more than twodecades. Mild to moderate alcoholconsumption—defined as one to threeglasses per day—is associated withlower mortality, reduced risk of coronary heart disease, and fewer white-matter lesions.1 Becausevascular disease is implicated in thecause of both vascular and Alzheimertype dementia, there has been renewedinterest in the role of alcohol, eventhough previous studies have beeninconclusive.

Studies done in the 1980s were cross-sectional in design, did not include possible confoundingcomorbid disorders, and producedconflicting results (odds ratios rangedfrom 0·5 to 2·3). Meta-analyses of these case control studies found nosignificant association between alcoholconsumption and dementia. However,the exclusion of individuals with ahistory of alcoholism or cardiovasculardisease was an important source ofbias in many of these studies. The factthat abstinence from alcohol iscommonly the result of poor health isanother potential source of bias. Inaddition, some studies did notdifferentiate between the type orquantity of alcohol consumed.

Several large-scale population-based studies, which accounted forboth confounding and interacting riskfactors in a longitudinal design, havenow been done. Most of these studieshave found an association of alcoholconsumption with a low risk ofincident dementia. More recentstudies have shown that risk is highboth in people who abstain fromdrinking and in those who consume alot of alcohol. The Rotterdamlongitudinal study2—which used“never drinkers” rather than recentabstainers as a reference group—concluded that risk was lowest inpeople who consumed one to threedrinks per day.

Non-health related variables mustalso be considered. Leibovici and co-workers3 reported a decrease risk of dementia (odds ratio=0·26)

associated with alcohol consumption.However, when place of residence wasincluded in the model used, this effectdisappeared. This is because elderlypeople with mild cognitive impair-ment or dementia commonly live innursing homes where alcohol isprohibited. Studies that do not takenon-alcohol related risk factors intoaccount are therefore at risk ofmisclassifying participants.

In a recent prospective nestedcohort study, Mukamal and co-workers4 have tried to avoid the biasesof previous studies. They tookrepeated measurements of alcoholconsumption, separated formerdrinkers from long-term abstainers,and tried to establish drinkingbehaviour up to 5 years before the startof the study. Mukamal and colleaguesalso attempted to obtain proxyassessment of deceased or unavailableparticipants.

The results of the study supportprevious findings of a small protectiveeffect of mild to moderate alcoholconsumption on the risk of dementia.However, out of 5888 participants inthe initial study, 842 were notexamined, 1386 did not have an MRIexamination, 52 did not complete acognitive examination, and 107 of 480incident cases of dementia wereeliminated. People with cognitiveimpairment and early dementia aremore likely to refuse cognitiveexaminations, to have difficulties intravelling to examination centres, andto drop out of community studies dueto change of residence. The authorsnoted, for example, that individualswho completed an MRI examinationwere significantly healthier andconsumed significantly more alcoholthan those who did not. Therefore, thisstudy may still have been open to bias.

The study by Mukamal and co-workers is an improvement onprevious studies for two reasons: first,the retrospective assessment ofcognitive function in deceasedindividuals by proxy questionnaire,although such a global assessmentwould cover all causes of terminalcognitive decline; and second, theassessment of drinking behaviour up

to 5 years before the start of the studyfor the identification of individualswho may have recently stoppeddrinking due to cognitive or otherhealth problems.

But is a 5 year time periodsufficient? Because dementia in laterlife has been associated with highblood pressure in early adulthood,5 doyounger adults who are at a high riskof developing dementia reduce theiralcohol consumption at an early agebecause of hypertension?

Although most population-basedstudies have found that consumptionof one to three glasses of alcohol perday decreases the risk of dementia inlater life, these findings should be interpreted with great caution.Population-based studies are flawed byvarious problems: the diagnosis ofincident dementia, the reliability ofself-reports of alcohol consumption,fluctuating patterns of drinkingbehaviour throughout life, mortality,and drop-out bias. More importantly,if alcohol is protective, at what age is it protective? Researchers haveassumed that alcohol is protectiveimmediately before the potential onsetof dementia. However, considering the adverse effects of alcoholconsumption—such as stroke, corticalatrophy, driving accidents, and falls—clinicians should think carefully beforeprescribing several glasses of alcoholper day in the absence of a clearbenefit.

Karen Ritchie

Institut National de la Santé et de laRecherché Médicale, E0361Epidemiology of Nervous SystemPathologies, Hôpital La Colombière,Montpellier, France. Email [email protected]

References1 Scherr PA, LaCroix AZ, Wallace RB. Light to

moderate alcohol consumption and mortality in theelderly. J Am Geriatr Soc 1992; 40: 651–57.

2 Ruitenberg A, van Swieten JC, Witteman JC, et al.Alcohol consumption and risk of dementia: theRotterdam study. Lancet 2002; 359: 281–86.

3 Leibovici D, Ritchie K, Ledésert B, Touchon J. The effects of wine and tobacco consumption oncognitive performance in the elderly: a longitudinalstudy of relative risk. Int J Epidemiol 1999; 28:77–81.

4 Mukamal KJ, Kuller LH, Fitzpatrick AL, LongstrethWT, Mittleman MA, Siscovick DS. Prospectivestudy of alcohol consumption and risk of dementiain older adults. JAMA 2003; 289: 1405–13.

5 Skoog I, Lernfelt B, Landahl S, et al. 15 yearlongitudinal study of blood pressure and dementia.Lancet 1996; 347: 1141–45.